Survival, Nonrelapse Mortality, and Relapse-Related Mortality After Allogeneic Hematopoietic Cell Transplantation: Comparing 2003-2007 Versus 2013-2017 Cohorts

Abstract

Background: Allogeneic hematopoietic cell transplantation is indicated for refractory hematologic cancer and some nonmalignant disorders. Survival is limited by recurrent cancer and organ toxicity.

Objective: To determine whether survival has improved over the past decade and note impediments to better outcomes.

Design: The authors compared cohorts that had transplants during 2003 to 2007 versus 2013 to 2017. Survival outcome measures were analyzed, along with transplant-related complications.

Setting: A center performing allogeneic transplant procedures.

Participants: All recipients of a first allogeneic transplant during 2003 to 2007 and 2013 to 2017.

Intervention: Patients received a conditioning regimen, infusion of donor hematopoietic cells, then immunosuppressive drugs and antimicrobial approaches to infection control.

Measurements: Day-200 nonrelapse mortality (NRM), recurrence or progression of cancer, relapse-related mortality, and overall mortality, adjusted for comorbidity scores, source of donor cells, donor type, patient age, disease severity, conditioning regimen, patient and donor sex, and cytomegalovirus serostatus.

Results: During the 2003-to-2007 and 2013-to-2017 periods, 1148 and 1131 patients, respectively, received their first transplant. Over the decade, decreases were seen in the adjusted hazards of day-200 NRM (hazard ratio [HR], 0.66 [95% CI, 0.48 to 0.89]), relapse of cancer (HR, 0.76 [CI, 0.61 to 0.94]), relapse-related mortality (HR, 0.69 [CI, 0.54 to 0.87]), and overall mortality (HR, 0.66 [CI, 0.56 to 0.78]). The degree of reduction in overall mortality was similar for patients who received myeloablative versus reduced-intensity conditioning, as well as for patients whose allograft came from a matched sibling versus an unrelated donor. Reductions were also seen in the frequency of jaundice, renal insufficiency, mechanical ventilation, high-level cytomegalovirus viremia, gram-negative bacteremia, invasive mold infection, acute and chronic graft-versus-host disease, and prednisone exposure.

Limitation: Cohort studies cannot determine causality, and current disease severity criteria were not available for patients in the 2003-to-2007 cohort.

Conclusion: Improvement in survival and reduction in complications were substantial after allogeneic transplant. Relapse of cancer remains the largest obstacle to better survival outcomes.

Primary funding source: National Institutes of Health.

Figure 1.

Comparison of outcomes of hematopoietic cell transplantation, 2003-2007 vs. 2013-2017 cohorts. Day-200 non-relapse mortality is displayed in A, relapse or progression of malignancy in B, relapse-related mortality in C, and overall mortality in D. Dotted lines in each figure represent the unadjusted estimates of the appropriate outcome, solid lines represent adjusted estimates. Adjusted estimates were derived by assuming a population in the 2003-2007 cohort that is consistent with the 2013-2017 population with respect to source of stem cells, donor type, disease severity, patient/donor sex, patient/donor CMV serostatus, comorbidity index, patient age, and conditioning intensity. Abbreviations: NRM, Non-Relapse Mortality; RRM, Relapse-Related Mortality.

Figure 1.

Comparison of outcomes of hematopoietic cell transplantation, 2003-2007 vs. 2013-2017 cohorts. Day-200 non-relapse mortality is displayed in A, relapse or progression of malignancy in B, relapse-related mortality in C, and overall mortality in D. Dotted lines in each figure represent the unadjusted estimates of the appropriate outcome, solid lines represent adjusted estimates. Adjusted estimates were derived by assuming a population in the 2003-2007 cohort that is consistent with the 2013-2017 population with respect to source of stem cells, donor type, disease severity, patient/donor sex, patient/donor CMV serostatus, comorbidity index, patient age, and conditioning intensity. Abbreviations: NRM, Non-Relapse Mortality; RRM, Relapse-Related Mortality.

Figure 1.

Comparison of outcomes of hematopoietic cell transplantation, 2003-2007 vs. 2013-2017 cohorts. Day-200 non-relapse mortality is displayed in A, relapse or progression of malignancy in B, relapse-related mortality in C, and overall mortality in D. Dotted lines in each figure represent the unadjusted estimates of the appropriate outcome, solid lines represent adjusted estimates. Adjusted estimates were derived by assuming a population in the 2003-2007 cohort that is consistent with the 2013-2017 population with respect to source of stem cells, donor type, disease severity, patient/donor sex, patient/donor CMV serostatus, comorbidity index, patient age, and conditioning intensity. Abbreviations: NRM, Non-Relapse Mortality; RRM, Relapse-Related Mortality.

Figure 2.

Comparison of daily laboratory values in conventional units for total serum bilirubin (A), serum creatinine (B), and serum albumin (C), 2003-2007 vs. 2013-2017. Restricted cubic spline curves are fit to the observed data (see Appendix, Supplementary Statistical Methods). Factors for conversion to SI units are 17.1 for total serum bilirubin, 88.4 for serum creatinine, and 10 for serum albumin.

Figure 2.

Comparison of daily laboratory values in conventional units for total serum bilirubin (A), serum creatinine (B), and serum albumin (C), 2003-2007 vs. 2013-2017. Restricted cubic spline curves are fit to the observed data (see Appendix, Supplementary Statistical Methods). Factors for conversion to SI units are 17.1 for total serum bilirubin, 88.4 for serum creatinine, and 10 for serum albumin.